Blood-surface interactions result in extensive hematological alterations which include release of vasoactive hormones and hydrolytic enzymes from platelets and leukocytes. These agents may mediate the increase in pulmonary vascular permeability frequently seen in a variety of clinical settings. Using enzyme, clotting and radio-immuno assays, we propose to measure the concentrations of the lyosomal markers B glucuronidase and lysozyme, prostaglandins E and F and bradykinin which appear in plasma during recirculation of 500 ml of fresh heparinized blood in a circuit consisting of silicone rubber tubing and venous reservoir and a spiral coil membrane oxygenator. We will then perfuse an isolated, in-situ, innervated canine lung with the above circuit to determine if these hydrolytic enzymes and permeability agents will cause pulmonary endothelial injury manifested by increases in pulmonary vascular and airway resistance and an increase in extravascular lung water. We will also measure prekallikrein, prekallikrein inhibitor, factor VIII levels, fibrin degredation products and fibrinogen patterns after gel filtration in our circuit and in the venous effluent of our perfused lung to determine the extent to which the injured lung potentiates surface induced hematological changes by interacting with the plasma proteolytic system (factor VIII fibrinogen) or secreting additional vasoactive hormones (prostaglandins, kinins). Finally we will add the reversible inhibitor, prostaglandin E1, to the venous reservoir of our circuit to prevent adverse hematological and pulmonary alterations by temporarily inhibiting platelets and white cells during contact with the foreign surface. This program of studies will serve to further evaluate the effects of artificial surfaces on blood with particular attention to potential mediators of lung injury. It will establish the injured lung's capacity to potentiate hematological changes and evaluate the efficacy of platelet and white cell inhibition as a therapeutic modality.